Stem cells are initial cells characterized by their ability to renew themselves and their potency to be differentiated into a diverse range of specialized functional cell type. Under specific conditions, stem cells can also be proliferated and differentiated into different functional cells. Therefore, studies on stem cells play an important role in renewment and traumatism repairment of tissues and organs in organisms, and may become the only hope for many incurable diseases, especially diseases related to loss or damage of cells and tissues. Stem cells include embryonic stem cells and adult stem cells. Application of embryonic stem cells is greatly restricted due to ethical issues. Since adult stem cells can be differentiated into functional cells and tissues, they provide the basis for wide application of stem cells, provide a good model in vitro for studies on early development of mammals, provide new sources for cell replacement therapies of many diseases, and also represent that development of modern biology and development of new drugs enter a new era. Thus, adult stem cells become the focus of scientific studies. However, normal adult mammalian stem cells are very few and are in resting state, and they are very hard to differentiate into one specific cell type since the differentiation and development thereof depend on multiple factors such as inner regulation mechanisms and micro-environments. It is hard to large-scale culture them in vitro for a long term, especially to culture and amplify them under serum free conditions. Thus, they cannot be applied to actual treatments. So far, only a few adult tissue stem cells can be cultured and amplify in vitro under serum free conditions, but, different growth factors, signaling molecules and the like need to be added to perform genetic regulation. Obviously, more effective and more selective cell culture materials and induction techniques are required in autologous and in vitro directed induction of proliferation and differentiation of stem cells so as to generate specific type of homologous cell population.
Many diseases can trace back to lost or damaged functional cells, and cell replacement therapy is an effective and sometimes, even the only method for treatment of these diseases. Cell replacement therapy is classified into cell transplantation and regulation of proliferation and directed differentiation of autologous stem cells by medicines. Stem cell drugs is a class of therapeutic and preventive medicines capable of preventing and treating diseases caused by loss or damage of cells by regulating stem cell proliferation and differentiations in organisms. It is found in recent years that both growth factors and small molecular compounds can regulate the proliferation and differentiation of stem cells in organisms. Application of stem cell drugs to regulate proliferation and potency of directed differentiation of autologous stem cells so as to rebuild the damaged functional cells and recover their biological function, not only solves the difficulty on the source of adult stem cell, but also avoids the ethical issues of embryonic stem cells as well as these problems involving cell transplantation immune rejection and post-surgical complications, and provides a completely new viewpoint and strategy for the treatment and prevention of diseases related to the lost or damaged functional cells.
For example, central nervous system diseases—neural degenerative or damaged disease, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), drug abuse, depression, cerebral apoplexy and the like, all of which are caused by loss and damage of neural cells. An ideal treatment strategy is to save damaged neural cells as much as possible and at the same time to stimulate regeneration of the neural cells. Currently, the damaged cells are tried to be repaired by transplantation of neural stem cells. However, there is a limitation on the obtainment of neural stem cells and functional cells for transplantation in clinic, as well as problems such as the ones involving cell transplantation immune rejection and post-surgical complications. Therefore, people have to focus on stimulation of proliferation and differentiation of autologous neural stem cells so as to provide the possibility of renewing the neural stem cells, and further to promote the development of neural stem cell drugs.
Growth factors or biologically active proteins can be used as stem cell drugs. However, growth factors or biologically active proteins as active micromolecule not only interferes with complicated physiological process to exhibit complicated multiple regulation functions, but also initiate immune response as heterologous peptides or proteins. Moreover, they are expensive and hardly have clinical treatment and medicinal use. Small molecular compounds are primary drugs in clinic for the treatment of diseases all the time, and people pay more and more attention to them because of their potential as stem cell regulation medicines.
Small molecular compounds include synthetic small molecular compounds and natural small molecular compounds (which mainly refer to compounds extracted from plants and active components of herbs). By comparison, small molecular medicines have the following characteristics and advantages.
a. For regulation resulted from small molecular compounds, the small molecular compounds are not only easy to be administrated, but also easy to be removed after recover of the physiological function, which is convenient for regulation of pathogenic and physiological process.
b. Unlike endogenous macromolecular active substances, which interfere with complicated multiple control systems in vivo and are easy to initiate immune response, exogenous small molecular compounds generally have a single regulation effect, and therefore are helpful for the retainment of normal physiological functions in organisms.
c. Small molecular compounds are easy to be artificially synthesized, and have a better medicinal value and clinic value in treatment than endogenous active macromolecular.
d. Especially natural small molecular compounds have a better biological adaptability, particularly lower toxicity as compared to the synthetic small molecular compounds as they have underwent biological (plant) metabolism.
e. Small molecular compounds are easy to cross blood brain barrier due to their small molecular weight.
Therefore, it is not only a hotspot in biological studies on in vitro proliferation and differentiation of adult stem cells but also a hotspot in studies on inventive drugs development—stem cell drugs to search small molecular compounds capable of specifically regulating adult stem cells proliferation and differentiation.
The purpose of the invention is to provide the small molecular compounds capable of accelerating proliferation of stem cells. The small molecular compounds can be used as stem cell proliferation accelerators and be used to prepare medicines accelerating stem cell proliferation, and provides more options for scientific research, clinic and medicines. Application of stem cell drugs to regulation of the proliferation and the potency of specific differentiation of autologous stem cells so as to rebuild the damaged functional cells and recover their biological functions, not only solves the difficulty relating to the source of adult stem cells, but also avoids the ethical restrictions of embryonic stem cells as well as the problem involving cell transplantation immune rejection and post-surgical complications, which provides new prospect and strategy for preventing and treatment of diseases related to the lost or damaged cells.